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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 901 records · Page 50Linked to original sources

The influence of calciotrophic hormones on lymphocyte transformation and interleukin-2 production in human mononuclear cells.

Peripheral blood mononuclear cells (PBMC) display receptors for parathyroid hormone (PTH) and calcitonin (CT) and, when activated, express receptors for 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). The role of these receptors in unclear. It is well established that 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) has a significant effect on lymphocyte transformation and interleukin-2 (IL-2) activity in PBMC's. We have proceeded to compare the effects of the calciotrophic hormones, 1,25(OH)2D3, 24,25 dihydroxyvitamin D3 (24,25(OH)2D3), 25 dihydroxyvitamin D3 (25(OH)D3), bovine (1-35)PTH (b(1-35)PTH) and salmon CT on both lymphocyte transformation and IL-2 activity in PBMC's from normal human volunteers. We have also sought an indication as to which subset of cells is responsible for the 1,25(OH)2D3 effect. Unlike the other calciotrophic hormones 1,25(OH)2D3 inhibited the proliferation of phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) stimulated cells. 1,25(OH)2D3 had a significantly greater effect on PHA induced cell proliferation and only inhibited cells with the T-helper/inducer (TH, CD4 + ve) phenotype, this suggested that 1,25(OH)2D3 may act selectively on the cells with CD4 + ve phenotype. In addition, of the calciotrophic hormones, 1,25(OH)2D3 had a greater effect on IL-2 activity. These findings indicate that 1,25(OH)2D3 and not the other calciotrophic hormones has a significant immunomodulatory effect.

24,25-Dihydroxyvitamin D 3↗

Preliminary investigation of alterations in blood viscosity, cellular composition, and electrophoresis plasma protein fraction profile after competitive racing activity in Thoroughbred horses.

In this preliminary investigation, various hematologic variables potentially influential in determining the degree of blood viscosity were evaluated in 10 Thoroughbred horses subjected to competitive acute running exercise. Following completion of sprints over a distance of 1.25 miles, mean percent (+/- SD) increases in PCV (38.3 +/- 12.9%), RBC (47.8 +/- 15.3%), and rouleaux index (232.7 +/- 176.8%) were recognized. Simultaneous increases in total plasma protein (28.3 +/- 5.31%), serum albumin (26.7 +/- 6.80%), alpha 1-globulin (60.0 +/- 49.0%), alpha 2-globulin (25.5 +/- 27.9%), beta 1-globulin (46.7 +/- 21.1%), beta 2-globulin (35.0 +/- 50.6%), gamma 1- and 2-globulins (38.7 +/- 29.6%), and plasma fibrinogen (12.5 +/- 10.4%) concentrations increased simultaneously. Horses also had consistent decreases in albumin:globulin ratio (-10.0 +/- 7.43%). Alterations in these hematologic values after acute running exercise in Thoroughbred horses accompanied increases in serum (69.3 +/- 39.7%), plasma (39.7 +/- 11.9%), and blood (134.7 +/- 55.3%) viscosity.

Animals↗

Vectors, promoters, and expression of genes in chick embryos.

Transgenic chickens were produced by injecting the Day-1 egg with 10(5) infectious particles of a replication-competent virus based on the Schmidt-Ruppin A strain of Rous sarcoma virus. The chickens were resistant to transforming subgroup A virus containing the src gene but not the corresponding subgroup B virus. Transgenic chickens producing bovine growth hormone (bGH) were generated using a modified virus containing the Bryan high titre polymerase gene. The virus was constructed with the bGH gene and the mouse metallothionein promoter in the reverse orientation relative to the viral structural genes. Two male chickens produced serum concentrations of approximately 100 ng bGH/ml; the birds were larger than controls and matured more rapidly. Transgenic mice required for the analysis of skeletal muscle-specific expression in vivo were produced using 5'-flanking regions of the chicken alpha-skeletal actin promoter linked to a luciferase reporter gene to determine the region essential for tissue-specific expression. The defined promoter sequences are to be used in experiments designed to direct expression of growth-promoting genes in skeletal muscle of chickens.

Animals↗

Drug-induced changes of plasma gastrin concentration.

There is a significant inverse relationship between intragastric acidity and plasma gastrin concentration. All generally available gastric acid antisecretory drugs induce a release of gastrin into the circulation. The more potent the gastric antisecretory dosage regimen or drug, the greater the rise of plasma gastrin concentration. The drug-induced rise of plasma gastrin concentration is of no direct clinical concern, although it may be partly responsible for the phenomenon of tolerance to H2-blockade. Drug-induced hypergastrinemia could stimulate the proliferation of certain cell lines associated with the gastrointestinal tract, for example, the gastric epithelium, ECL cells, or colonic neoplasms.

Adenocarcinoma↗

The avian neural crest as a model system for the study of cell lineages.

Under the influence of environmental factors, the neural crest gives rise to numerous cell types and is therefore, by definition, a pluripotential structure. However, it was not clear until recently to what extent each individual neural crest cell possessed multiple capacities for differentiation. As a result of in vivo and in vitro approaches aimed at solving this problem, it has become apparent that the neural crest is made up of cells in different states of determination and that some lineages are segregated very early. In particular, analysis of clones obtained from single cells grown in culture has shown that, although many individual neural crest cells are pluripotential to varying degrees, others are apparently committed to give rise to only one derivative. The role of the embryonic microenvironment in the emergence of phenotypic diversity is probably complex, certain factors acting to promote the survival of selected subpopulations of fully determined progenitors, while others may direct partly committed precursors towards a specific developmental fate.

Animals↗

A controlled, double-blind study of the effect of quazolast on nasal challenge with ragweed antigen.

Quazolast is a potent mediator release inhibitor as determined by in vitro and in vivo testing. A placebo-controlled, double-blind, two-way crossover study compared the safety and efficacy of Quazolast, 400 mg bid orally, with placebo in 23 subjects with ragweed (RW) allergy, out of season. Subjects were assigned to two 7-day treatments in a random sequence with an 8-day washout. Subjects were challenged on days 1 and 7 of each trial with serial dilutions (10, 100, 1000, 1350, and 2700 PNU/0.135 mL) of RW, using metered pump spray bottles, (two sprays delivered 0.135 mL), preceded by saline control. Efficacy evaluation consisted of nasal flow rates measured by rhinomanometry, sneeze counts, nasal itchiness scores, and weight of nasal secretions during challenges. During Quazolast treatment, subjects had significantly lower (P less than .05) mean percent decreases in nasal flow rate at 1350 and 2700 PNU. Nasal itchiness scores were significantly lower (P less than .05) during Quazolast treatment than at placebo at 1000, 1350, and 2700 PNU. Although sneeze counts were lower during treatment with Quazolast than with placebo, the results did not reach statistical significance. No significant improvement was seen in the weight of nasal secretions. Adverse experiences, clinical laboratory results, and physical examinations were unremarkable, posttreatment. Quazolast was superior to placebo in protecting against nasal congestion and nasal itchiness after ragweed nasal challenge.

Adult↗

Lithium clearance in healthy humans: effects of sodium intake and diuretics.

In summary, our experiments clearly demonstrate that lithium reabsorption occurs by frusemide- and bumetanide-sensitive reabsorption, but we have failed to identify the mechanism(s) responsible for the lower CLi and FELi in salt-depletion. It is possible that some, as yet unknown, factor increases the activity of the Na, K, 2Cl cotransporter and, hence, increases lithium reabsorption in the thick ascending limb in salt-depleted subjects. However, it is equally possible that a fraction of proximal tubular reabsorption is inhibited by frusemide and bumetanide. If this is correct, CLi in humans are reasonable markers of proximal tubular function even in conditions of avid salt retention and in salt depletion, when fractional reabsorption of salt and water in the proximal tubules is enhanced.

Amiloride↗

Heparin monitoring in the coronary care unit after percutaneous transluminal coronary angioplasty.

The rate of acute restenosis in patients after percutaneous transluminal coronary angioplasty (PTCA) is related to thrombotic complications triggered by the PTCA. This risk is reduced by anticoagulating the patients with heparin after the procedure. The anticoagulation state of patients receiving heparin therapy is routinely monitored with the activated partial thromboplastin time (APTT) test. In an effort to provide more timely results regarding the status of patients who are receiving heparin after PTCA, a study was conducted to see whether low-range activated clotting time measurement (LR ACT) performed at the bedside could provide information comparable to that from APTT values determined in the laboratory. The study showed that the LR ACT values were comparable to laboratory-generated APTT values (R2 = 0.68). The LR ACT data generated were superior to the APTT data in terms of timeliness and the wider range of heparin levels covered. Having these values available allowed the CCU staff to react rapidly to changes in the patient's coagulation status.

Angioplasty, Balloon, Coronary↗

Thrombosis in human pancreatic transplantation associated with elevated cyclosporine levels and possible protection by antihypertensive agents.

Acute thrombosis in human pancreatic transplantation (HPT) remains a serious problem occurring in 10% to 30% of many reported series. Thrombosis may result from a number of causes including technical error, acute rejection, or low-flow states secondary to conditions within the host or in the transplanted organ. Evidence accumulates suggesting cyclosporine (CSA) acts as a potent vasoconstricting agent and that antihypertensive medications such as calcium channel blocking agents may offer protection from this effect. We have reviewed 68 consecutive human pancreatic transplants at the University of Iowa, specifically evaluating CSA levels, and the use or nonuse of antihypertensive medications. We found CSA levels in patients with transplant thrombosis to be elevated above the mean in 80% of patients with levels available 24 hours prior to thrombosis. Fifty percent of these (CSA) levels were well above one standard deviation. In addition, those patients receiving routine antihypertensive medication (most commonly calcium channel blocking agents) were statistically less likely to have thrombosis of the pancreatic transplant. We suggest that elevated levels of CSA may play at least a partial role in thrombosis of HPT and antihypertensive agents may offer protection from this effect.

Adult↗

Development of brachytherapy technique for nasal tumors in dogs.

Two groups of 4 dogs underwent nasal and ethmoidal turbinectomies followed by irradiation (mean minimal) doses of 5,390 and 6,550 cGy of radiation, respectively) from implanted intracavitary sources of iridium 192. Two dogs from each group were euthanatized for histologic evaluation at 3 months after irradiation. The remaining 2 dogs from each group were euthanatized for similar evaluation at 6 months after irradiation. During the course of the study, few clinical complications were encountered. Histologic evaluation of the tissues forming the nasal passages revealed loss of epithelial lining and fibrous tissue replacement of surrounding bone. A direct correlation of pathologic changes could not be associated with the amount of radiation received, but there seemed to be a tendency for greater change in those dogs given higher doses and those kept alive for 6 months.

Animals↗

EXAFS studies of the isolated bovine heart Rieske [2Fe-2S]1+(1+,2+) cluster.

Recently the involvement of one or, more likely, two nitrogen-ligands in the Rieske-type [2Fe-2S] cluster has been reported based on the chemical assay and various spectroscopic analyses, such as EPR, Mössbauer, ENDOR, and resonance Raman, of isolated Thermus thermophilus HB-8 protein by Fee and his collaborators. Similarly, the presence of at least one nitrogen ligand was shown in the mitochondrial Rieske [2Fe-2S] cluster. We have conducted EXAFS studies of the Rieske [2Fe-2S] protein isolated from the cytochrome bc1 complex of bovine heart mitochondria. Standard analysis could not distinguish one or two nitrogen ligands per cluster. However, one nitrogen and three cysteine ligands per cluster was found to be, possibly, a better solution in more comprehensive analysis procedures.

Animals↗